Such measurement devices are widely used in various branches of industry for example in the Pharmaceutical Industry, in Biotechnology, as well as in Medicine. They are for example used for measurements of physical properties of products processed in bioreactors in Life Science Industry.
There is a wide range of physical properties that need to be measured or monitored in these application, including for example a temperature of a product, a conductivity of a product, or analytical properties of a product, such as a pH value, an Oxygen content, an oxidation reduction potential or a content of a specific ion. These physical properties are typically measured using commercially available measurement probes comprising corresponding sensing elements. During measurement, the probe is inserted into a measurement chamber containing the product and the physical property is measured.
In these branches of industry very high standards of hygiene are required. These standards may vary slightly from country to country, but in general they require that any surfaces of the measurement arrangement which may come in contact with the product can be effectively cleaned and/or sterilized.
In conventional measurement arrangements of this type, e.g. in bioreactors, closed systems are used. They comprise stainless steel vessels and the measurement probes are inserted through metal ports into these vessels. The closed system is sterilized by hot steam or chemicals for a period of time to assure that all living organisms are inactivated. The bioreactor is then cooled, dried and charged for example with media, cells, nutrients and gasses and the bioreaction is started. Since the measurement probe was sterilized with the initial sterilization cycle of the measurement arrangement, the probe coming into contact with the bioreaction media through the sidewall of the bioreactor is sterile. Electronic signals from the measurement probe are for example used to precisely control the physical property measured therewith.
In order to avoid the time and costs involved in sterilizing the closed system these Industries may prefer to use pre-sterilized disposable measurement arrangements comprising disposable containers and disposable measurement devices.
The main advantage of disposable measurement arrangements is, that cleaning and sterilization of the equipment is no longer necessary at the site where the Pharmaceutical, Biotech or Medical processing takes place. Disposable, pre-sterilized components and systems can be kept in stock. This allows for a great time efficiency, especially when production lines need to be set up, enlarged or scaled down frequently.
Today, there is a wide range of disposable containers on the market. They are for example manufactured by companies such as HyClone, Logan, Utah, USA or Sartorius BBI Systems GmbH, Germany. Disposable single use containers usually comprise a large flexible bag with sterile connections for the attachment of tubing. The empty disposable containers are typically sterilized with gamma radiation and delivered to the customer. The customer attaches sterile tubing to the container via the sterile connections which allow for the pre-sterilized components to be connected together without breaching sterility of the system or individual components.
There are many types of sterile connectors on the market. They allow for two separate sterile elements to be connected without breaching sterility. The elements are for example disposable tubes, pipes or containers each comprising means for a sterile connection. The elements to be connected are sterilized at the suppliers facilities and the sterile connections prevent breach of sterility of the sterile elements during shipment and storage of the sterile elements.
One commonly used type of sterile connector is for example sold by Pall Corporation, New York, USA under the trade name Kleenpak®.
These single use connectors allow for a dry connection of two separate fluid pathways, while maintaining the sterile integrity of both. The connection is made by a male connector located on the first element and a female counter connector located on the second element to be connected. Each connector is covered by a vented peel away strip that protects the port and maintains the sterility of the sterile pathway inside the respective elements. The two elements are connected by aligning the connector and the counter connector such that the peel away strips are facing each other. In a next step the connector and the counter connector are interconnected, for example snapped together. At this stage, the two peel away strips are pressed against each other between the two connectors. They both comprise an end section, which extends outside the two connectors. The two peel away strips sealing the passageway are removed simultaneously by pulling them out by their end sections. By removing these seals simultaneously, the passageway is cleared without breaching the sterility of the interior of the two elements to be connected and of the passageway connecting them.
Another type of sterile connections is promoted by Wave Biotech, which is part of GE Healthcare Bioscience Bio Process Corporation, New Jersey, USA. In this type of connection, the two elements to be connected together have a tubular shape. The end of each tubular element is thermally welded closed and both elements are sterilized. Both elements to be joined together are inserted into a holder such that their ends overlap. A sterile hot blade or knife is inserted into the holder and cuts through both elements, thus cutting of the overlapping sealed ends. Then the tubular elements are realigned inside the holder and pushed together to engage in a sealed sterile connection.
In order to measure physical properties of a medium inside a measurement chamber, it is possible, to pre-install corresponding measurement probes on disposable measurement arrangements, for example on disposable containers of the type mentioned above, and to sterilize the measurement probe together with the container using gamma radiation.
This requires however, that the entire measurement arrangement is pre-assembled and sterilized prior to its use. All the required measurement probes need to be known and provided beforehand. In many applications however, it is necessary to respond quickly and efficiently to changing needs. This is not possible when pre-assembled measurement arrangement are use. They cannot for example be adapted to changing measurement requirements. Once the measurement arrangement has been sterilized, it is not possible to change or add measurement probes without breaching sterility of the arrangement.